Trypanocidal activity of copaiba oil and kaurenoic acid does not depend on macrophage killing machinery

Danielle Kian; César Armando Contreras Lancheros; João Paulo Assolini; Nilton Syogo Arakawa; Valdir Florêncio Veiga-Júnior; Celso Vataru Nakamura; Phileno Pinge-Filho; Ivete Conchon-Costa; Wander Rogério Pavanelli; Sueli Fumie Yamada-Ogatta; Lucy Megumi Yamauchi

doi:10.1016/j.biopha.2018.04.164

Trypanocidal activity of copaiba oil and kaurenoic acid does not depend on macrophage killing machinery

Biomed Pharmacother. 2018 Jul:103:1294-1301. doi: 10.1016/j.biopha.2018.04.164. Epub 2018 May 7.

Affiliations

¹ Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil.
² Departamento de Ciências Básicas da Saúde, Centro de Ciências da Saúde, Universidade Estadual de Maringá, Maringá, PR, Brazil.
³ Departamento de Ciências Patológicas, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil.
⁴ Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Estadual de Londrina, Londrina, PR, Brazil.
⁵ Departamento de Química, Instituto de Ciências Exatas, Universidade Federal do Amazonas, Manaus, AM, Brazil.
⁶ Departamento de Microbiologia, Centro de Ciências Biológicas, Universidade Estadual de Londrina, Londrina, PR, Brazil. Electronic address: lionilmy@uel.br.

PMID: 29864911
DOI: 10.1016/j.biopha.2018.04.164

Abstract

Activity, mechanisms of action, and toxicity of natural compounds have been investigated in a context in which knowledge on which pathway is activated remains crucial to understand the action mechanism of these bioactive substances when treating an infected host. Herein, we showed an ability of copaiba oil and kaurenoic acid to eliminate Trypanosoma cruzi forms by infected macrophages through other mechanisms in addition to nitric oxide, reactive oxygen species, iron metabolism, and antioxidant defense. Both compounds induced an anti-inflammatory response with an increase in IL-10 and TGF-β as well as a decrease in IL-12 production. Despite being able to modulate the immune response in host cells, the antimicrobial activity of copaiba oil and kaurenoic acid seems to be a direct action of the compounds on the parasites, causing their death.

Keywords: Anti-inflammatory effect; Antimicrobial activity; Chagas disease; Copaiba oil; Kaurenoic acid.

MeSH terms

Animals
Antiprotozoal Agents / pharmacology*
Cell Proliferation / drug effects
Diterpenes / pharmacology*
Down-Regulation / drug effects
Down-Regulation / genetics
Fabaceae / chemistry*
Ferritins / genetics
Ferritins / metabolism
HeLa Cells
Heme Oxygenase-1 / genetics
Heme Oxygenase-1 / metabolism
Humans
Interleukin-10 / genetics
Interleukin-10 / metabolism
Interleukin-12 / genetics
Interleukin-12 / metabolism
Macrophages, Peritoneal / drug effects
Macrophages, Peritoneal / enzymology
Macrophages, Peritoneal / metabolism*
Macrophages, Peritoneal / parasitology
Male
Mice, Inbred BALB C
Models, Biological
NF-E2-Related Factor 2 / genetics
NF-E2-Related Factor 2 / metabolism
Nitric Oxide / metabolism
Nitric Oxide Synthase Type II / genetics
Nitric Oxide Synthase Type II / metabolism
Nitrites / metabolism
Oils, Volatile / pharmacology*
Reactive Oxygen Species / metabolism
Transforming Growth Factor beta / genetics
Transforming Growth Factor beta / metabolism
Trypanosoma cruzi / drug effects*
Tumor Necrosis Factor-alpha / genetics
Tumor Necrosis Factor-alpha / metabolism

Substances

Antiprotozoal Agents
Diterpenes
NF-E2-Related Factor 2
Nitrites
Oils, Volatile
Reactive Oxygen Species
Transforming Growth Factor beta
Tumor Necrosis Factor-alpha
Interleukin-10
Interleukin-12
Nitric Oxide
kaurenoic acid
Ferritins
Nitric Oxide Synthase Type II
Heme Oxygenase-1